Warfarin is a potent anticoagulant agent which is known to inhibit the enzyme vitamin K epoxide reductase. The molecular mechanism of inhibition is not known. We have proposed a mechanism-based inactivation of this enzyme by Warfarin and other oral anticoagulants. Experiments have been desgined to study the mechanism of action of vitamin K epoxide reductase unsing chemical model studies and known and new inhibitors of this enzyme. Radiactively-labeled substrate analgoues will be used and metabolites identified in order to gain information about the enzyme mechanism. Our understanding of this enzyme mechanism will be used to determine the molecular mechanism of some known oral anticoagulants as well as to form the basis for the design of new inhibitors having potential anticoagulant activity.